Carbamylated vimentin represents a relevant autoantigen in Latin American (Cuban) rheumatoid arthritis patients.
Carbamylated vimentin represents a relevant autoantigen in Latin American (Cuban) rheumatoid arthritis patients.
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DOI：
10.1007/s00296-016-3472-9
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发表时间：
2016-06
影响因子：
4
通讯作者：
Feist E
中科院分区：
文献类型：
--
作者：
Martínez G;Gómez JA;Bang H;Martínez-Gamboa L;Roggenbuck D;Burmester GR;Torres B;Prada D;Feist E
吸烟通过蛋白质的翻译后氨甲酰化产生激活促炎、促血栓形成和血管收缩介质的物质。作为氨甲酰化的一个新结果，在类风湿关节炎（RA）患者中观察到抗氨甲酰化自身抗体的诱导，有时在疾病发作之前。本研究的总体目的是表征不同同种型自身抗体对波形蛋白氨甲酰化抗原的反应性，这些抗体与已建立的类风湿因子（RF）、抗瓜氨酸蛋白抗体（ACPA）和疾病活动标志物有关，这些标志物在迄今为止基本上未表征的拉丁美洲（古巴）RA患者人群中。在101例RA患者、50例疾病对照和51例健康对照中分析了氨甲酰化波形蛋白以及波形蛋白肽的抗原特性。将诊断性能与已建立的商业ELISA类风湿因子、第二代抗环瓜氨酸肽抗体（抗CCP 2）和抗突变瓜氨酸波形蛋白（抗MCV）抗体进行比较。在该RA队列中，抗MCV IgG（86%）、抗氨甲酰化波形蛋白（carbVIM）IgG（77%）和抗氨甲酰化MCV（carbMCV）IgG抗体（65%）的患病率高于经典RF IgM（60%）和抗CCP 2 IgG（52%）。值得注意的是，吸烟状态与75.0%的患者中抗CCP 2和90%的患者中抗MCV的阳性IgG抗体反应性相关。此外，在80%和90.0%的吸烟者中分别观察到针对carbMCV和carbVIM的IgM抗体应答。由于抗carbVIM IgM抗体同种型的灵敏度高达85.2%，ACPA与抗carbVIM IgM的组合提供了迄今为止在该种族RA队列中实现的最佳诊断性能。我们证明了高患病率的抗carbVIM抗体和吸烟在拉丁美洲（古巴）RA患者的相关性。抗carbVIM IgM是ACPA阴性患者的一种有用标志物，与ACPA IgG检测试剂结合使用，可优化自身抗体检测策略。本文的在线版本（doi：10.1007/s 00296 -016-3472-9）包含补充材料，可供授权用户使用。
Smoking produces substances that activate proinflammatory, prothrombotic and vasoconstrictive mediators via posttranslational carbamylation of proteins. As a new consequence of carbamylation, induction of anti-carbamylated autoantibodies were observed in rheumatoid arthritis (RA) patients, sometimes prior to onset of the disease. The overall aim of this study was to characterize the reactivity of different isotypes of autoantibodies against carbamylated antigens of vimentin in relation to established rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA) and markers of disease activity in a so far largely uncharacterized population of Latin American (Cuban) patients with RA. Antigenic properties of carbamylated vimentin as well as vimentin peptides were analyzed in 101 patients with RA, 50 disease controls and 51 healthy controls. The diagnostic performance was compared with established commercial ELISA rheumatoid factor, anti-cyclic citrullinated peptide antibodies of second generation (anti-CCP2) and anti-mutated citrullinated vimentin (anti-MCV) antibodies. Prevalence of anti-MCV IgG (86 %), anti-carbamylated vimentin (carbVIM) IgG (77 %) and anti-carbamylated MCV (carbMCV) IgG antibodies (65 %) was higher than the classical RF IgM (60 %) and anti-CCP2 IgG (52 %) in this RA cohort. Of note, smoking status was associated with positive IgG antibody reactivity against CCP2 in 75.0 % and against MCV in 90 % of patients. Furthermore, IgM antibody response against carbMCV and carbVIM was observed in 80 and 90.0 % of smokers, respectively. Due to a high sensitivity of the IgM antibody isotype of anti-carbVIM of 85.2 %, the combination of ACPA with anti-carbVIM IgM provided the best diagnostic performance so far achieved in a RA cohort of this ethnic origin. We demonstrate a high prevalence of anti-carbVIM antibodies and correlation with smoking in Latin American (Cuban) RA patients. Anti-carbVIM IgM represents an useful marker in ACPA-negative patients and, in combination with ACPA IgG assays, optimizes the strategy for autoantibody testing. The online version of this article (doi:10.1007/s00296-016-3472-9) contains supplementary material, which is available to authorized users.